Sarcoidosis and chronic berylliosis are chronic granulomatous fibrotic diseases that share striking clinical and histopathologic features as well as local (lung) and systemic immune abnormalities. The objective of this study is to conduct parallel studies of these diseases in order to elucidate the immunopathogenetic events. There are four interrelated areas of investigation. First, to characterize the phenotypic identity and function of immune effector cells that can be recovered from sites of inflammatory involvement (lung) and blood. These studies will be conducted in a serial prospecitve fashion to determine if there is a relationship between these studies and progression of resolution of disease. Second, we will test the hypothesis that antibodies to T lymphocytes, which have been previously described, alter the number, identity or function of immune regulatory T cells and contribute to the immune abnormalities observed in sarcoidosis. A third related area is the study of the accessory cell function for lung (alveolar macrophages) and blood macrophages in these patients. This will examine the role of macrophages in influencing the degree of activation and function of immunoregulatory T cells found in the lung. Specifically, macrophage functions, such as the release of Interleukin-1 and effect on lymphocyte proliferation, will be examined. The final aim of the proposal will be to develop in vitro systems for the stimulation and long-term cultivation of antigen reactive T cell clones for both diseases. This will take advantage of the fact that there is an accumulation of activated T cells in the lung and that preliminary studies indicate that, utilizing T cell growth factor, the establishment of continous T cell lines is feasible in both diseases. We will attempt to develop in vitro assays for antigen-specific T cell clones with the use of antigen (beryllium salts and standardized preparation of Kveim antigens) and autologous accessory feeder cells. The long-term goal of this component of the study will be to develop an in vitro assay for the Kveim antigen and begin to identify the putative antigens that may be contained in the Kveim preparations. These investigations are part of a long-range interest in interstitial and fibrotic lung diseases and are a component of the Interstitial Lung Disease Program (and Sarcoidosis Clinic) at the Hosp. of Univ. of Pa.